Possible AIDS cure found

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The startling case of an AIDS patient who underwent a bone marrow transplant to treat leukemia is stirring new hope that gene-therapy strategies on the far edges of AIDS research might someday cure the disease.

The patient, a 42-year-old American living in Berlin, is still recovering from his leukemia therapy, but he appears to have won his battle with AIDS. Doctors have not been able to detect the virus in his blood for more than 600 days, despite his having ceased all conventional AIDS medication. Normally when a patient stops taking AIDS drugs, the virus stampedes through the body within weeks, or days.
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More : http://online.wsj.com/article/SB122602394113507555.html

Sounds like you need to block CCR5 to defeat AIDS :eek:
 
well, now they need to narrow down on a thousand factors that might have been responsible. poor guy will be anally probed for years.

btw there are plenty of cases of people having HIV immunity.
 
People on drugs like Maraviroc (Selzentry) and newer drugs like Vicriviroc still develop resistance and end up succumbing to HIV unless they can subsist on combinations of other anti-HIV drugs (ARVs). Mutations in HIV GP120 allow it to
resist the Chemokine CoReceptor 5 moleculer antagonists through this mechanism or
via the virus no longer requiring the CCR5 receptor (non-CCR5 tropism).

You can read more about Maraviroc here:
http://hivinsite.ucsf.edu/InSite?page=ar-06-01

The other issue is that HIV doesn't only invade CD4 lymphocytes but also cells called
macrophages and various other cells including cells in the gut and brain, which can
serve as a reservoir.

So fluke or they may still find HIV RNA in the patient encoded in its dormant DNA
form.

Contrary to what lay people think, no one ever gets anally probed by the scientific/medical community. Anal probing
is the domain of 1. Border security and 2. Sci-fi alien abductions. :)
 
phenom said:
wait, so the virus may actually mutate somewhere and resist ccr5?

lol, i think he meant, anal(as in strict) probing (as in the media keeping an eye here and there issue), em yha, the use of rhetoric lol. guess thats why he wanted to be a doc

pwned u NM
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CCR5 is the molecule MOST of the HIV uses to enter cells together with CD4
receptors, at least in the early stages of the HIV infection.
Drugs - namely the CCR5 inhibitors (which have been around for a couple of years now) such as Maraviroc and Vicriviroc are able to bind to the CCR5 molecule on CD4 lymphocytes (white cells) and so prevent entry of the virus.
However, through mutations in the virus GP120 protein which interacts with these receptors OR through the virus using an alternative route of entry into
the cell (which often happens later in the course of the infection) the virus
may still enter the CD4 cells despite the CCR5 being blocked.

An alternative molecule which may be the target for anatagonism (blockage)
is CXCR4 but blockers of this molecule have not been successful or safe thus far, it is thought that CXCR4 may be essential for other regulatory processes and blocking it can be harmful in itself. Still, there is research going on in this field.

Drugs which block these receptors (and others) are called
Entry Inhibitors.
http://en.wikipedia.org/wiki/Entry_inhibitors

Problem with HIV is that it loves to mutate. It's copying facilities (enzymes)
are so bad that if two people become infected by the same person,
after a while the two HIV viruses present in each of these 2 persons,
will be genetically different, which is also a reason why two HIV positive people should
still wear protection or abstain from sex with each other.
HIV mutations are the chief cause of resistance of the HIV to Anti-HIV drugs.

Still CCR5 antagonists (blockers) are proving to be effective in SALVAGE therapy (when other agents have proven to be ineffective) or in combination
with other drugs to CONTROL HIV. The Research continues.....
 
phenom said:
So the more we shoot it, it comes back even stronger?


Does this mean that there is no hope for a quick drug?

Our only hope? Nanobots?

Can't we gimmick the virus to enter fake cells we injected, then have them stuck, trapped and destroyed by the fake cells? Then take all the ARV's, and CCR5 blocking drugs, to flush the system of the virus? Then repeat this process on and on. injecting cloned white bloodcells, if that is possible.

The question remains, would we ever really be able to totally cure this virus away? Making a person, completely clear?

It's like we'd need a whole-body transplant, and above that still take a few ARV's after that to hunt down the few that may still lie in the brain.

point: how will we ever get rid of a disease that keeps changing?
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Well there isn't really any feasible conceptual idea yet of curing someone.

The virus encrypts its genetic code into various body cells, that is the problem. The second problem is that this virus mutates (hence the reason why people are treated with 3 anti-HIV drugs at any one time to limit this
mutation to allow for treatment for a reasonable period of time).

Nanotechnology? Maybe, nothing being researched in that field at present.
(That is in HIV and nanotech).

Whole bone marrow transplants are very dangerous. They are used to treat leukemias but that's when they're your only option for survival and you often need a good genetic match. There are lots of dangers with these procedures
so curing HIV with them does not seem like a way to go.

Anyway at present the research is heading towards new drugs and classes and reinforcement of older drugs plus the concept of therepeutic vaccines.
While preventative vaccines have been a failure thus far, there is some hope
that they may work in the future - however their development requires time - years. Preventative vaccines won't cure HIV infection though. Therapeutic
vaccines are being researched at present. It is believed that taking these vaccines after someone is infected with HIV with lower the viral 'set point'
this is the amount of HIV present in the blood while the virus is sleeping
in the early stages of virus infection. The lower the setpoint the longer the life expectancy and time till one has to take ARV meds.

There are other dangers however. With more people on ARV there are risks that more 'wild type' virus (that's the virus found in newly infected people who haven't been on ARV) will be resistant to some ARVs. Already with the ARVs
used to prevent spread of HIV from mother to unborn child at labour, already
with that there are questions and concerns coming up about this causing a degree of wild resistance to Nevirapine and AZT (the two ARV drugs used in
prevention of spread of HIV from mother to child). The more people use
ARV the more wild type virus will be resistant. As is even without ARV usage
some wild type viruses are resistant to some drugs already!
 
Souped-up immune cells catch even disguised HIV

WASHINGTON, Nov. 9, 2008 (Reuters) — Genetically engineered immune cells can spot the AIDS virus even when it tries to disguise itself, offering a potential new way to treat the incurable infection, researchers reported on Sunday.

The killer T-cells, dubbed "assassin" cells, were able to recognize other cells infected by HIV and slow the spread of the virus in lab dishes.

If the approach works in people, it might provide a new route of treating infection with the deadly human immunodeficiency virus, the researchers in the United States and Britain said.

"Billions of these anti-HIV warriors can be generated in two weeks," said Angel Varela-Rohena of the University of Pennsylvania, who helped lead the study.

In a second, unrelated report, researchers testing Dutch biotechnology firm Crucell NV's experimental AIDS vaccine said it prevented infection in six monkeys.

The animals were infected with a monkey version of HIV called SIV, and the vaccine used a virus that is dangerous to use in humans, so it is not ready for human tests.

But, writing in the journal Nature, Dr. Dan Barouch of Beth Israel Deaconess Medical Center and Harvard Medical School in Boston and colleagues said it shows there is still hope for developing a vaccine against AIDS.

The AIDS virus, which infects 33 million people globally, is especially hard to fight. Like all viruses, it hijacks cells in its victims, forcing them to become little viral factories and make more virus.

ESCAPE AND EVADE

HIV is even more insidious, attacking immune system cells called CD4 T cells, which help mount a defense. It can also disguise itself to escape CD8 killer cells, also known as cytotoxic T lymphocytes or CTLs.

"CTLs are crucial for the control of HIV infection. Unfortunately, HIV has an arsenal of mutational and nonmutational strategies that aid it in escaping from the CTL response mounted against it by its host," the researchers wrote in their report, published in the journal Nature Medicine.

One good defense allows HIV to hide a protein called HLA-I-associated antigen.

Varela-Rohena and colleagues took T-cells from an HIV patient and created a genetically engineered version that recognizes this deception.

"It is possible to improve on nature when it comes to preventing HIV CTL escape," they wrote.

Not only could the engineered T-cells see HIV strains that had escaped detection by natural T-cells, "but the engineered T cells responded in a much more vigorous fashion so that far fewer T-cells were required to control infection," Penn's James Riley, who also worked on the study, said in a statement.

"In the face of our engineered assassin cells, the virus will either die or be forced to change its disguises again, weakening itself along the way," added Andy Sewell of Britain's Cardiff University.

Perhaps having to mutate will weaken the virus, the researchers said.

They plan to test the T-cell treatment in HIV patients next year.

"We have managed to engineer a receptor that is able to detect HIV's key fingerprints and is able to clear HIV infection in the laboratory," said Bent Jakobsen, chief scientific officer at Adaptimmune Ltd, a British company launched in July that owns the rights to the technology. "If we can translate those results in the clinic, we could at last have a very powerful therapy on our hands."
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http://www.newsdaily.com/stories/tre4a8343-us-aids-killers/
 
Thanks PeterCH for the info. Going to read a bit more about CCR3 and CXCR4...:p

There is also some pretty impressive research going on at Wits were they are trying to silence gene expression (after HIV integration) by using riboswitches, hairpin RNAs and other forms of gene silencing. That way, even if you get infected, the virus may be kept under control.
Interesting presentation
Current research at Wits
 
Last edited:
*sigh*

Jacob Zuma found the cure for AIDS - in his bathroom.
 
Phronesis said:
Thanks PeterCH for the info. Going to read a bit more about CCR3 and CXCR4...:p

There is also some pretty impressive research going on at Wits were they are trying to silence gene expression (after HIV integration) by using riboswitches, hairpin RNAs and other forms of gene silencing. That way, even if you get infected, the virus may be kept under control.
Interesting presentation
Current research at Wits
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Thanks for the link. Looks good. :)
 
OT - Having gone through the thread, it's good to see there is some focus on curing HIV and not enabling people to live with it. Albeit, they are a bit extreme, I mean can you imagine the chemo for zapping most of your system away, AND go through a bone marrow transplant process. All the while with a 30% chance of death. Scary.

But I think some people would go for it.
 
sox63 said:
OT - Having gone through the thread, it's good to see there is some focus on curing HIV and not enabling people to live with it. Albeit, they are a bit extreme, I mean can you imagine the chemo for zapping most of your system away, AND go through a bone marrow transplant process. All the while with a 30% chance of death. Scary.

But I think some people would go for it.
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It's not available as treatment. It may never be.
 
phenom said:
Whole-body transplant (or brain-transplant, into a clone) is the only answer i see! Not only for AIDS, but for almost all other diseases and illnesses too. No it's not as far fetched as it sounds.
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Many of the problems are in the brain.

I think by the time we figured out how to clone people successfully, and transplant brains, we will have figured out alternatives to this too.
 
http://www.amfar.org/cgi-bin/iowa/programs/resrch/record.html?record=71

A First Step Toward a Cure for AIDS? Novel Procedure Appears to Have Eliminated HIV

By Jeffrey Laurence, M.D.

November 5, 2008—We need a cure for AIDS. We can’t treat our way out of this epidemic. Anti-HIV therapy is a lifelong commitment, accompanied by many life-altering and some potentially life-threatening side effects. And for every person placed on treatment, two to three are newly infected. In 2007 alone there were 2.7 million new infections, and only 31 percent of those who needed treatment received it. Viral reservoirs—cells and tissues in which HIV remains dormant, beyond the reach of anti-HIV drugs but poised to grow at any moment—persist for the life of an infected person. And while all currently available anti-HIV drugs suppress the virus, they cannot eliminate it.

Given this context, a brief report in February 2008 by a group of physicians from Germany appeared to change everything when presented as a poster at the annual Conference on Retroviruses and Opportunistic Infections in Boston. It described a 40-year-old man—an American working in Berlin—whose HIV had been under good control for several years using a typical cocktail of drugs known as HAART. Then he developed acute leukemia.

In an attempt to cure the leukemia, he underwent a course of radiation therapy and chemotherapy in preparation for a stem cell transplant. But in his case, rather than simply using the best match among available stem cell donors, his physicians did something very clever. They also screened potential donors for a natural mutation known as delta32 CCR5. CCR5 is the primary means by which most types of HIV infect cells. Individuals lacking this CCR5 receptor—the 1.5 percent of the Caucasian population in America and Europe with the delta32 mutation—are completely resistant to infection by the most common forms of HIV.

The patient’s stem cell transplant was a success, although relapse of his leukemia required a second transplant using the same donor. Now off all anti-HIV drugs for almost two years, the patient continues to show no detectable signs of HIV in his blood, bone marrow, lymph nodes, intestines, or brain. To the limits of our ability to detect HIV, it appears that the virus has been eradicated from his body. At the very least this patient represents a functional cure: he is off all anti-HIV meds, has a normal T-cell count, and exhibits no evidence of virus.

amfAR quickly called together 10 experts in clinical AIDS, stem cell transplantation, and HIV virology for a two-day think tank at the MIT Endicott House to evaluate these data. The patient’s physician, Gero Hutter, presented details of the case, which were closely scrutinized by all. In a summary statement, attendees indicated that this case does indeed represent at least a functional cure. Dr. Hutter agreed to ask his patient to provide additional blood samples so that scientists attending the amfAR meeting could perform even more sensitive tests to attempt to further document that the virus has been erased from the patient. amfAR is coordinating distribution of these samples.

But amfAR’s involvement doesn’t end there. It is possible that the patient may have been cured of HIV/AIDS. But the cost of such a stem-cell transplant procedure can run up to $250,000. It is associated with a relatively high death rate from infectious and immunologic complications, and the number of delta32-CCR5 donors of appropriate tissue type would be very small. Here further research may yield key answers.

For example, it is unknown whether the use of a delta32-CCR5 donor is essential. Perhaps the transplant procedure itself was the most important element. The potential to genetically engineer stem cells to remove CCR5 from a patient’s own stem cells also exists, and strategies to do so were discussed at the think tank. These and related issues will serve as topics for an upcoming amfAR grant cycle.

Read the Wall Street Journal's article on these research findings by clicking here.

Dr. Laurence is amfAR’s senior scientific consultant.
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